A common denominator of patients with the acquired immune deficiency syndrome (AIDS) appears to be a broad spectrum of immune deficiencies. However, it is clear that we continue to lack the full understanding of the mechanism(s) responsible for this immunologic dysfunction. We have initiated a study to examine whether peripheral blood lymphocytes from AIDS patients evidence a pattern of in vitro CMI response against mitogens and against specific viral antigens (CMV, HSV, BKV), in relation to disease progression, in vivo data generated by skin testing, and data generating by enumeration of T cell subsets as observed over a period of time. The ability to reconstitute the in vitro CMI response to specific viral antigens and mitogens will be measured by treatment with biologic modifiers such as IL-1, II-2 and other lymphokines. Lastly, plasma from AIDS patients is examined to determine whether it contains immunosuppressive factors to normal T lymphocytes in the above assays, and whether these factors can be modified or detected through plasmaphoresis. In preliminary studies, 10 homosexual men with lymphadenopathy and 10 homosexual men with AIDS have been studied longitudinally. AIDS patients (8 with opportunistic infection and two with Kaposi's sarcoma) and all lymphadenopathy patients were skin test anergic, had reversed T helper/T suppressor cell ratios with prominent T helper cell depletion, and demonstrated hypergammaglobulinemia and elevated immune complexes. Healthy homosexual men and patients with lymphadenopathy responded to pokeweed mitogen and viral antigens in lymphocyte transformation studies and these responses were enhanced to control levels with the addition of interleukin-2. Significantly, lymphadenopathy patients lacked the ability to produce lymphokine-leukocyte migration inhibition factor (LIF) following antigen stimulation. This latter finding correlated with in vivo energy in all instances. Patients with AIDS demonstrated a marked reduction in lymphocyte transformation response to pokeweed mitogen and a total absence of responsiveness to viral antigen. Lymphocyte transformation was partially restored by interleukin-2 in this latter instance. However, the ability to restore antigen induced responsiveness by IL-2 markedly decreased with disease progression, and lymphokine production remained negative. These data thus far demonstrate a gradient of immune dysfunction that develops in AIDS and further study is warranted in regards to the exact nature of the immunosuppressive factors and their effect on immune regulation as measured by lymphokine IL-1 and IL-2.